Anterior gradient-2 (AGR2) was first found by differential screening in a human breast cancer cell line with estrogen receptor expression (Kuang, W. W., et al., Nucleic Acids Res, 1998. 26(4): p. 1116-23), and subsequently, its full-length cDNA clone was obtained. After comparison, it was found to be homologous to a toad XA-2 development associated protein and was designated as hAG-2 (Thompson, D. A. and R. J. Weigel, hAG-2, Biochem Biophys Res Commun, 1998. 251(1): p. 111-6). AGR2 has a high homology with protein disulfide isomerase (PDI) (Persson, S., et al. Mol Phylogenet Evol 2005 36(3): p. 734-40), and has PDI activity (Park, S. W., et al., PNAS, 2009. 106(17): p. 6950-5). AGR2 has the PDI active site “CXXS”, which is distinguished from the normal PDI site “CXXC”. Through studies on other PDI proteins, it has been indicated that the “CXXS” active site has the function of disulfide bond rearrangement, but lacks the function of synthesizing the disulfide bond. That means that AGR2 has the function of disrupting the normal growth of cells but lacks the ability to recover their functions. (Anelli, T., et al., EMBO J, 2002. 21(4): p. 835-44. Anelli, T., et al., EMBO J, 2003. 22(19): p. 5015-22).
AGR2 is a marker protein for primary and secondary tumors, is detectable in the circular system of patients with a tumor, and is closely associated with the development and metastasis of tumors. AGR2 has the effect of promoting the transformation and migration of breast cancer cells (Liu D, et al. Cancer Res, 2005, 65(9): 3796-3805). AGR2 can increase the invasive ability of pancreatic cancer cells, thereby promoting the metastasis of the tumor (Ramachandran V, et al. Cancer Res, 2008, 68(19): 7811-7818). AGR2 plays a crucial role in the metastasis of prostate cancers (Zhang Y, et al. Cancer Res, 2010, 70(1): 240-248). It was not until 2010 that Kathryn et al. mentioned that AGR2 polyclonal antibody can inhibit the growth of breast cancer cells (Kathryn E Vanderlaag, et al. breast cancer, 2010, 12).